B7-h3 as a biomarker for diagnosing the progression and early lymph node metastasis of cancer

Abstract

B7H3 is a ligand member of the immunoregulatory family of proteins on immune cells. In one embodiment, a method for diagnosing the progression of cancer with a high propensity of primary tumor metastasis to the lymph node or distant site is provided. Such a method may comprise obtaining a cancer tissue sample from a cancer patient, determining an expression level of B7-H3 present in the tissue sample, and diagnosing the progression of the cancer having a high propensity of primary tumor metastasis to the lymph node or distant site based upon the expression level, wherein an increased expression level correlates with an increased probability of having regional lymph nodes or organ site that are positive for metastases.

1 . A method for diagnosing the progression of cancer with a high propensity of primary tumor metastasis to the lymph node or distant site comprising:
 obtaining a cancer tissue sample from a cancer patient; and   determining an expression level of B7-H3 present in the tissue sample; and   diagnosing the progression of the cancer having a high propensity of primary tumor metastasis to the lymph node or distant site based upon the expression level, wherein an increased expression level correlates with an increased probability of having regional lymph nodes or organ site that are positive for metastases.   
     
     
         2 . The method of  claim 1 , wherein the cancer tissue sample is a primary or metastatic tumor tissue specimen. 
     
     
         3 . The method of  claim 2 , wherein the expression level of B7-H3 is determined by immunohistochemistry. 
     
     
         4 . The method of  claim 2 , wherein the expression level of B7-H3 is determined by a direct qRT-PCR assay. 
     
     
         5 . The method of  claim 1 , wherein the cancer tissue sample is a blood specimen from a cancer patient. 
     
     
         6 . The method of  claim 5 , wherein the expression level of B7-H3 is determined by an anti-B7-H3 magnetic bead capture assay. 
     
     
         7 . The method of  claim 5 , wherein the expression level of B7-H3 is determined by a direct qRT-PCR assay. 
     
     
         8 . The method of  claim 6  or  7 , wherein the assay detects B7-H3 expressed on circulating tumor cells. 
     
     
         9 . The method of  claim 1 , wherein the cancer is selected from the group consisting of melanoma, breast cancer, gastrointestinal cancers such as gastric cancer, colorectal, periampullary, pancreatic, liver cancer. 
     
     
         10 . The method of  claim 1 , wherein the cancer is melanoma. 
     
     
         11 . The method of  claim 1 , wherein the cancer is breast cancer. 
     
     
         12 . A method for predicting nodal metastasis in breast cancer comprising:
 obtaining a primary breast cancer tumor tissue sample from a breast cancer patient; and   determining an expression level of B7-H3 present in the primary breast cancer tumor tissue sample;   diagnosing progression of breast cancer wherein an increase in the B7-H3 expression level correlates with an increase in the number of lymph nodes having metastases.   
     
     
         13 . The method of  claim 12 , further comprising: obtaining a lymph node tissue from a breast cancer patient; and determining the expression level of B7-H3 present in the lymph node. 
     
     
         14 . The method of  claim 12 , wherein the expression level of B7-H3 is determined by immunohistochemistry. 
     
     
         15 . The method of  claim 12 , wherein the expression level of B7-H3 is determined by qRT-PCR or any quantitative or binary molecular detection assays for B7-H3. 
     
     
         16 . The method of  claim 12 , further predicting primary tumor size, wherein an increase in the B7-H3 expression level correlates with an increase in tumor size. 
     
     
         17 . The method of  claim 12 , further predicting AJCC stage of breast cancer, wherein an increase in the B7-H3 expression correlates with a higher stage. 
     
     
         18 . A method for predicting the progression of melanoma cancer comprising
 obtaining a melanoma tumor tissue sample; and   determining an expression level of B7-H3 present in the melanoma tumor tissue sample; and   diagnosing progression of melanoma, wherein an increase in B7-H3 expression correlates with an increase in primary tumor tissue metastasis.   
     
     
         19 . The method of  claim 18 , wherein the expression level of B7-H3 is determined by immunohistochemistry. 
     
     
         20 . The method of  claim 18 , wherein the expression level of B7-H3 is determined by qRT-PCR, or any quantitative or binary molecular detection assays for B7-H3 
     
     
         21 . A method for detecting circulating tumor cells in a cancer patient, comprising:
 obtaining a bodily fluid sample from a cancer patient;   performing an assay to detect the presence of a B7-H3 expression level in the bodily fluid sample, wherein a higher expression level of B7-H3 correlates with a higher number of circulating tumor cells.   
     
     
         22 . The method of  claim 21 , wherein the bodily fluid sample is selected from the group consisting of blood, cerebrospinal fluid (CSF), spinal fluid, synovial fluid, ascetic fluid, pericardial fluid and peritoneal fluid. 
     
     
         23 . The method of  claim 21 , wherein the assay is qRT-PCR. 
     
     
         24 . The method of  claim 21 , wherein the assay is an anti-B7-H3 magnetic bead capture assay. 
     
     
         25 . A method for treating a cancer with a high propensity of primary tumor metastasis to the lymph node or distant site comprising:
 obtaining a bodily fluid sample from a cancer patient;   detecting the presence of a population of B7-H3-positive CTC in the bodily fluid; and   administering a therapeutically effective amount of a pharmaceutical composition, the pharmaceutical composition comprising a B7-H3 ligand conjugated to a cytotoxic drug;   wherein the pharmaceutical composition kills B7-H3 circulating tumor cells and prevents metastasis.   
     
     
         26 . The method of  claim 25 , wherein the bodily fluid is selected from the group consisting of blood, cerebrospinal fluid (CSF), spinal fluid, synovial fluid, ascetic fluid, pericardial fluid and peritoneal fluid. 
     
     
         27 . The method of  claim 25 , wherein detection of a population of B7-H3-positive CTC is accomplished by performing qRT-PCR on the bodily fluid sample. 
     
     
         28 . The method of  claim 25 , wherein detection of a population of B7-H3-positive CTC is accomplished by performing an anti-B7-H3 magnetic bead capture assay. 
     
     
         29 . The method of  claim 25 , wherein the B7-H3 targeted therapy is a B7-H3 ligand conjugated with a cytotoxic drug.